Hassing J M, Padmanabhan V, Kelch R P, Brown M B, Olton P R, Sonstein J S, Foster C M, Beitins I Z
Department of Pediatrics, University of Michigan Hospitals, Ann Arbor 48109-0718.
J Clin Endocrinol Metab. 1990 Apr;70(4):1082-9. doi: 10.1210/jcem-70-4-1082.
The microheterogeneity and bioassayable activity of serum FSH (B-FSH) can be regulated by exogenous GnRH in boys with idiopathic hypogonadotropic hypogonadism and by estrogen in a women with gonadal dysgenesis, presumably via hormonally mediated changes in the degree of FSH glycosylation. To test the hypothesis that testosterone (T) regulates the circulating forms of B-FSH, we raised the serum T levels of early pubertal boys to adult levels. In this model, high dose T inhibits the pubertal nocturnal augmentation of LH secretion, apparently through decreased GnRH secretion. This model allowed us to test a second hypothesis, that B-FSH is a sensitive indicator of hypothalamic GnRH release. The boys were studied on two consecutive weekends, during which they received either saline (S) or T infusions. Beginning at noon on the study day, after an overnight acclimatization, the boys received either S or T at 33% or 100% of the adult male production rate. Blood was sampled from 2000-0800 at 10-min intervals for immunoactive LH and FSH (I-FSH) and for B-FSH, as determined by the in vitro Sertoli cell aromatase induction assay, and at 30-min intervals for T. Gonadotropin levels were analyzed as mean hourly or 3-h concentrations and as pulse profiles by two established objective peak detection programs, Cluster and Detect. During S treatment, mean LH increased after the onset of sleep (P = 0.0006) and, after plateauing for several hours, declined to baseline in the early morning hours. Mean levels of B-FSH were also minimally (but significantly) increased after the onset of sleep (P = 0.046) and paralleled the decline noted for LH. Mean levels of I-FSH did not demonstrate a diurnal rhythm. The effect of T was gonadotropin specific. High dose T abolished the nocturnal elevation in mean LH concentrations, but had no effect on the nocturnal elevation of B-FSH (P less than 0.05) or on I-FSH levels. The LH pulse frequency was greatest from 2300-0450 h, during S treatment (P = 0.016). The pulse frequency of B-FSH was also minimally increased after the onset of sleep (P = 0.045). The T infusion abolished the nocturnal increase in LH pulse frequency, without an effect on B-FSH pulse frequency. B-FSH pulse frequency exceeded LH pulse frequency during S treatment (8.0 +/- 0.7 pulses/12 h vs. 5.5 +/- 0.4), and B-FSH pulses persisted throughout the night. The pulse amplitudes of LH and B-FSH were not affected by T.(ABSTRACT TRUNCATED AT 400 WORDS)
特发性低促性腺激素性性腺功能减退男孩的血清促卵泡生成素(B - FSH)的微异质性和生物活性可受外源性促性腺激素释放激素(GnRH)调节,而性腺发育不全女性的血清促卵泡生成素则受雌激素调节,推测是通过激素介导的促卵泡生成素糖基化程度变化来实现的。为验证睾酮(T)调节B - FSH循环形式的假说,我们将青春期早期男孩的血清T水平提高到成人水平。在这个模型中,高剂量T抑制青春期夜间促黄体生成素(LH)分泌的增加,显然是通过降低GnRH分泌来实现的。这个模型使我们能够验证第二个假说,即B - FSH是下丘脑GnRH释放的敏感指标。在连续两个周末对这些男孩进行研究,在此期间他们接受生理盐水(S)或T输注。在研究日中午开始,经过一夜适应后,男孩们以成年男性产生率的33%或100%接受S或T。从20:00至08:00,每隔10分钟采集血液样本,检测免疫活性LH和FSH(I - FSH)以及通过体外支持细胞芳香化酶诱导试验测定的B - FSH,每隔30分钟采集血液样本检测T。促性腺激素水平分析为每小时或3小时的平均浓度,并通过两个既定的客观峰值检测程序Cluster和Detect分析脉冲图谱。在S治疗期间,睡眠开始后平均LH增加(P = 0.0006),在达到平稳水平数小时后,在清晨时段降至基线。睡眠开始后B - FSH的平均水平也有轻微(但显著)增加(P = 0.046),并与LH的下降趋势平行。I - FSH的平均水平未显示出昼夜节律。T的作用具有促性腺激素特异性。高剂量T消除了夜间平均LH浓度的升高,但对B - FSH的夜间升高(P < 0.05)或I - FSH水平没有影响。在S治疗期间,LH脉冲频率在23:00至04:50最高(P = 0.016)。睡眠开始后B - FSH的脉冲频率也有轻微增加(P = 0.045)。T输注消除了夜间LH脉冲频率的增加,而对B - FSH脉冲频率没有影响。在S治疗期间,B - FSH脉冲频率超过LH脉冲频率(8.0±0.7次脉冲/12小时对5.5±0.4次脉冲/12小时),并且B - FSH脉冲整夜持续存在。LH和B - FSH的脉冲幅度不受T影响。(摘要截短至400字)